Pilot Study of Same-session MR-only Simulation and Treatment With MRI-guided Adaptive Palliative RadioTherapy (MAP-RT)
Phase: NA
Conditions: Malignancy, Metastasis, Hemoptysis, Gastrointestinal Bleeding, Pelvic Bleeding, Superior Vena Cava Syndrome, Mediastinal Disease
Sponsor: Washington University School of Medicine

Title:   
Pilot Study of Same-session MR-only Simulation and Treatment with 
MRI-guided Adaptive Palliative Radiotherapy 
 
NCT:   
 
NCT03824366 
 
Version Date: 
01/25/19 

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Pilot Study of Same-session MR-only Simulation and Treatment with MRI-
guided Adaptive Palliative Radiotherapy  
 
 
Washington University School of Medicine 
Department of Radiation Oncology 
660 South Euclid Avenue, Campus Box 8224 
St. Louis, MO  63110 
  
Protocol #: Pending 
Version Date: 01/25/19 
  
Principal Investigator:  
Hyun Kim, M.D. 
Phone:  (314) 362-8502 
E-mail:  kim.hyun@wustl.edu 
  
Sub-Investigators: 
 
Soumon Rudra, M.D. 
Lauren Henke, M.D., MSCI 
Olga Green, Ph.D. 
 
 
 
 
 
 
 
  
  
Clinical Trials.gov #:        
Pending         
  
  
CONFIDENTIAL 
The information contained in this document is regarded as confidential and, except to the extent necessary to 
obtain informed consent, may not be disclosed to another party unless law or regulations require such 
disclosure.  Persons to whom the information is disclosed must be informed that the information is 
confidential and may not be further disclosed by them 
 
 
 

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Pilot Study of Same-session MR-only Simulation and Treatment with 
Stereotactic MRI-guided Adaptive Palliative Radiotherapy 
 
Protocol Revision History 
 
Initial Approval Version 
 
 
 
 
 
 
mm/dd/yyyy 
Amendment #1 Version 
 
 
 
 
 
 
mm/dd/yyyy 
 
 
 

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Table of Contents 
1 
BACKGROUND ..................................................................................................................... 4 
1.1 
Palliative Radiotherapy .................................................................................................... 4 
1.2 
EBRT for Palliation .......................................................................................................... 4 
1.3 
MRgRT for Palliation....................................................................................................... 5 
1.4 
Rationale ........................................................................................................................... 6 
2 
OBJECTIVES .......................................................................................................................... 6 
2.1 
Primary Objective ............................................................................................................ 6 
2.2 
Exploratory Objectives ..................................................................................................... 6 
3 
ELIGIBILITY CRITERIA ...................................................................................................... 7 
3.1 
Inclusion Criteria .............................................................................................................. 7 
3.2 
Exclusion Criteria ............................................................................................................. 7 
3.3 
Inclusion of Women and Minorities ................................................................................. 7 
4 
REGISTRATION PROCEDURES ......................................................................................... 7 
4.1 
Confirmation of Patient Eligibility ................................................................................... 7 
4.2 
Patient Registration in the Siteman Cancer Center OnCore Database ............................. 8 
4.3 
Assignment of UPN ......................................................................................................... 8 
5 
RADIATION THERAPY GUIDELINES ............................................................................... 8 
5.1 
Dose, Fractionation .......................................................................................................... 8 
5.2 
Patient Positioning............................................................................................................ 8 
5.3 
Definitions ........................................................................................................................ 8 
5.4 
Same-session MR-only Simulation and Fraction 1 Treatment Planning ......................... 9 
5.5 
Quality Assurance of the Daily Treatment Plan ............................................................... 9 
5.6 
Follow Up ......................................................................................................................... 9 
6 
REGULATORY AND REPORTING REQUIREMENTS ................................................... 10 
6.1 
Definitions ...................................................................................................................... 10 
6.2 
Reporting to the Human Research Protection Office (HRPO) at Washington University
 
12 
6.3 
Reporting to the Quality Assurance and Safety Monitoring Committee (QASMC) at 
Washington University ............................................................................................................. 12 
6.4 
Timeframe for Reporting Required Events .................................................................... 12 
7 
STUDY CALENDAR ........................................................................................................... 13 
8 
DATA SUBMISSION SCHEDULE ..................................................................................... 13 
9 
DATA SAFETY AND MONITORING................................................................................ 13 
10 
STATISTICAL CONSIDERATIONS............................................................................... 14 
10.1 Sample Size Calculations ............................................................................................... 14 
10.2 Stopping Criteria ............................................................................................................ 14 
11 
REFERENCES .................................................................................................................. 16 
 
 

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1 
BACKGROUND 
 
1.1 
Palliative Radiotherapy  
 
Palliation of symptoms from metastatic cancer can be achieved by delivery of radiation 
therapy (RT)1. Emergent conditions with established evidence for palliative RT include 
critical cancer-induced symptoms such as hemoptysis2,3, gastrointestinal (GI) bleeding4,5, 
pelvic bleeding6–9, bulky mediastinal disease causing airway or vascular compression, and 
superior vena cava (SVC) syndrome2,10. Painful bony metastases may also require short 
courses of radiation to palliate symptoms that are refractory to narcotics. Oncology patients 
with these conditions frequently require inpatient hospitalization. They may have limited 
treatment options, given that such syndromes often indicate large burden of metastatic 
disease and/or disease progression despite prior therapies. In this setting, RT can palliate 
symptoms and potentially mitigate life threatening symptoms with minimal risk for 
toxicity.  
 
1.2 
EBRT for Palliation 
 
External beam RT (EBRT) has long been the approach of choice for such palliative 
treatments. The traditional workflow for a patient to receive palliative radiation using 
EBRT requires multiple steps including consultation with a radiation oncologist, computed 
tomography (CT) simulation for radiation therapy planning, quality assurance of the 
planned radiation course, and final approval of the plan by the radiation oncology 
physician. Given these numerous important steps, multiple delays in the treatment planning 
workflow can occur and result in delays to start of RT for patients requiring urgent therapy.  
 
At our clinic, the scarcity of available appointment times for CT simulation would result 
in delay of RT planning and delivery. Since delays are unacceptable in treating urgent 
cases, these patients may start RT without simulation, using simplified radiation planning 
performed with manual calculations for the first one or two fractions of treatment, while 
an opening in the CT simulation schedule is pending. These “clinical set-ups” consume 
significant time from the treatment team and result in both dose uncertainty and workflow 
inefficiency. Even when CT simulation is successfully performed for patients requiring 
urgent palliative RT, delivery of treatment using conventional linear accelerators may be 
limited with regards to imaging guidance for treatment setup accuracy. On board imaging 
for linear accelerators are limited to two-dimensional portal films or three-dimensional 
cone beam CTs both of which have difficulty in discriminating various soft tissue densities.  
 
The combination of clinical set-ups with lack of CT simulation data and poor soft-tissue 
resolution with on board imaging leads to use of larger treatment volumes to address spatial 
uncertainty, as well as dose uncertainty from manual calculations. This subsequently 
increases risk of toxicity. This is especially significant if upfront palliative doses are to be 
followed by definitive treatment doses. Clearly, there is a need for improvement in the 
radiation therapy workflow and image guidance for treatment delivery in patients who 
require urgent palliative RT.  
 

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1.3 
MRgRT for Palliation 
  
A solution may exist with the use of magnetic resonance image-guided radiotherapy 
(MRgRT). MRgRT involves RT delivery using an integrated MRI, radiotherapy device, 
and dedicated treatment planning system. MRI-guidance is performed with a 0.35 Tesla 
imaging unit while treatment is delivered through an integrated Cobalt-60 radiotherapy 
device or linear accelerator (LINAC). Imaging with MRgRT can be performed daily, using 
a 17 second or 172 second volumetric scan, with excellent soft-tissue contrast that is 
sufficient for real-time treatment planning and plan modification while the patient lies on 
the treatment table11,12. These daily treatment plans, typically created in response to 
changes in daily anatomy, are termed “adaptive radiotherapy” (ART). The MRI-guided 
ART treatment planning process includes nearly all components of traditional treatment 
planning for palliative RT, such as volumetric imaging, target volume delineation by the 
physician, treatment plan generation, and quality assurance with an independent, Monte 
Carlo-based dose verification11,13.   
 
However, the traditional treatment planning workflow for MRgRT is limited by the current 
need for pre-treatment MRI and CT simulation imaging, which provide data to select 
appropriate beam geometry and electron density information for dose calculation. The 
standard of care for electron density calculation is a CT scan of the patient in the treatment 
position and immobilization device that will be used for daily treatments. An ideal 
workflow for urgent palliative MRgRT would permit use of same session-MR imaging to 
generate a treatment plan while the patient is on the treatment table. In most instances, 
conventional urgent palliative RT plans use simple radiation beam arrangements and large 
field sizes to ensure target coverage. The traditional field arrangements are anterior-
posterior (AP) and posterior-anterior (PA) beam pairs, regardless of tumor site, which may 
treat large amounts of normal tissue. Use of pre-specified beam angles would mitigate the 
need for pre-treatment imaging to define beam geometry and improve the feasibility of 
creating the clinical plan in a time frame that is acceptable and tolerable for the patient to 
remain on the treatment table. Further, MRgRT allows real-time gating of tumor motion, 
so a significantly smaller amount of normal tissue would be treated by using MRgRT. 
 
Regarding CT-free treatment planning for MRgRT, some progress has been made towards 
this goal at other institutions. Investigators at the University of Wisconsin have used their 
MRgRT device for same-session simulation and treatment planning and delivery of the 
first fraction of 2D and 3D-conformal palliative spine radiation treatments. However, 
following the first treatment fraction, patients then underwent traditional CT simulation 
and treatment planning for treatment plan and dose verification; ART was used only to 
expedite the first fraction.  
 
In such treatment planning, bulk density overrides have been used to assign electron 
densities based on typical values for basic tissue types (bone, fat, lung, soft tissue)14. Bulk 
density overrides are an FDA-approved mechanism for dose extrapolation in MRgRT 
radiation planning, and can overcome the absence of CT density information15. Such 
overrides carry an anticipated dose uncertainty of <3%, which is considered acceptable 
especially in the setting of urgent palliative treatments16. For comparison, manual 

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calculations of dose such as those used in clinical setups rely only upon measurement of 
the patient width in the treatment plane (the patient “separation”), without correction for 
heterogeneity of internal structure composition. This approach, although frequently 
utilized in the first one to two fractions for urgent treatments, results in an average single-
fraction dose discrepancy between manually and computer-calculated dose of up to 10%, 
with uncertainty up to 25-30% for sites like the thorax where tissue density heterogeneity 
is substantial17,18. Although this uncertainty is then averaged out over the remaining 
treatment fractions following CT-simulation, the uncertainty of MR-only dose calculation 
using bulk density override may indeed be an improvement upon the cumulative dose 
uncertainty of a treatment course utilizing manual calculations for one or more treatment 
fractions. Additionally, the < 3% dose uncertainty incurred using bulk density override for 
MR-only planning is well within the AAPM Task Group 141 recommendation of ± 5% 
cumulative dose uncertainty19. 
 
1.4 
Rationale 
 
Given the availability of MRgRT technology and the growing clinical experience with MR-
only planning, we propose to evaluate the feasibility of same-session MR-only simulation 
and treatment with urgent palliative RT for patients with diagnosis of metastatic 
malignancy presenting with hemoptysis, GI bleeding, pelvic bleeding and bulky 
mediastinal disease/SVC syndrome. Although MRgRT has been used for palliative spine 
treatments previously at our institution, this expedited same-session MR-only simulation 
and treatment will include non-spine treatments. This proposed study is unique in that 
patients will not undergo CT simulation at any point during their treatment course and will 
instead have same-session MR-only simulation and treatment planning, on-table, using the 
ART workflow. In this manner, patients requiring urgent treatment could initiate treatment 
as early as the day of initial radiation oncology consultation.  
 
 
2 
OBJECTIVES 
 
2.1 
Primary Objective 
 
Demonstrate feasibility of same-session MRI-only simulation and treatment with MRI-
guided palliative radiation therapy for hemoptysis, GI bleeding, pelvic bleeding, and SVC 
syndrome/ bulky mediastinal disease. Feasibility will be defined as more than 70% of 
patients receiving at least 70% of their scheduled treatment fractions on the first on-table 
attempt for each respective fraction. 
 
2.2 
Exploratory Objectives 
  
1. Determine the proportion of patients who complete planned course of palliative 
radiation therapy.  
2. Determine the on-table time required for each component of same-session MRI-only 
simulation and treatment with plan generation for the initial treatment fraction and for 
subsequent treatment fractions. 
 

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3 
ELIGIBILITY CRITERIA 
 
3.1 
Inclusion Criteria 
 
1. Diagnosis of malignancy (biopsy proven or high clinical suspicion with 
urgent/emergent clinical indications for palliative RT) 
2. Requires delivery of palliative radiation therapy for the treatment of painful metastasis, 
hemoptysis, gastrointestinal bleeding, pelvic bleeding, or superior vena cava 
syndrome/bulky mediastinal disease.  
3. Has had or will have a diagnostic CT for the region being treated. 
4. At least 18 years of age. 
5. Able to understand and willing to sign an IRB-approved written informed consent 
document. 
  
3.2 
Exclusion Criteria 
 
1. Pregnant.  Patients of childbearing potential must have a negative pregnancy test within 
14 days of study entry. 
2. Medical contraindication to undergoing MR imaging. 
 
3.3 
Inclusion of Women and Minorities 
 
Both men and women and members of all races and ethnic groups are eligible for this trial. 
 
 
4 
REGISTRATION PROCEDURES 
 
Patients must not start any protocol intervention prior to registration through the Siteman 
Cancer Center. 
 
The following steps must be taken before registering patients to this study: 
 
1. Confirmation of patient eligibility 
2. Registration of patient in the Siteman Cancer Center OnCore database 
3. Assignment of unique patient number (UPN) 
 
4.1 
Confirmation of Patient Eligibility 
 
Confirm patient eligibility by collecting the information listed: 
 
1. Registering MD’s name 
2. Patient’s race, sex, and DOB 
3. Three letters (or two letters and a dash) for the patient’s initials 
4. Copy of signed consent form 
5. Completed eligibility checklist, signed and dated by a member of the study team 

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6. Copy of appropriate source documentation confirming patient eligibility 
 
4.2 
Patient Registration in the Siteman Cancer Center OnCore Database 
 
All patients must have registered through the Siteman Cancer Center OnCore database. 
 
4.3 
Assignment of UPN 
 
Each patient will be identified with a unique patient number (UPN) for this study.  All data 
will be recorded with this identification number on the appropriate CRFs. 
 
 
5 
RADIATION THERAPY GUIDELINES 
 
5.1 
Dose, Fractionation 
 
Radiation therapy dose and fractionation will be one of the following standard regimens: 
 8 Gy in 1 fraction 
 20 Gy in 5 fractions 
 30 Gy in 10 fractions 
 25 Gy in 5 fractions 
 37.5 Gy in 15 fractions 
 
Due to the palliative nature of treatments, radiation prescriptions may vary from single 
fraction regimens to fifteen fraction regimens.  
 
5.2 
Patient Positioning 
 
All patients will undergo volumetric MR imaging on treatment days in positioning 
appropriate for the specific treatment site. This will most frequently be supine with arms 
positioned so not in the way of treatment beams. 
 
5.3 
Definitions 
 
 Gross Tumor Volume (GTV) 
 
The GTV will be defined as the visible gross tumor on the volumetric MR imaging 
obtained on the first day of treatment. 
 
 Clinical Target Volume (CTV) 
 
The treating physician may choose to define a CTV based on clinical judgement 
(margin that accounts for microscopic disease), but this is not required. 
 

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 Planning Target Volume (PTV) 
 
If a CTV is created, the PTV is defined as a volumetric 5 to 10 mm margin 
expansion of the CTV (to account for setup error). If no CTV is created, the PTV 
is defined as a volumetric 5 to 20 mm margin expansion of the GTV.  
 
5.4 
Same-session MR-only Simulation and Fraction 1 Treatment Planning 
 
All patients will need to be screened with an MR screening questionnaire with clearance 
by MR level II staff prior to MR imaging. Prescription dose per fraction will be chosen 
from the above doses at the discretion of the treating physician. The protocol will not 
require segmentation of critical structures given the relatively low doses used during 
palliative radiation therapy. Coverage goal for the PTV will be for 95% of the volume to 
be covered by 95% of the dose.  
 
On the day of Fraction 1, each patient will be planned based on their MRI volumetric image 
set obtained during simulation. A bulk density override method will be used to manually 
assign relative electron density values to the MRI dataset for the purpose of dose 
calculation. Initial plan parameters may be generated based on diagnostic imaging. For 
example, voxels representing the patient’s bones will be assigned an average bone density, 
voxels representing fat will have a different density assignment, etc. On subsequent 
treatment fractions, another volumetric MRI image will be obtained on the treatment 
machine itself, and the plan will be adjusted based on anatomy and patient habitus of the 
day.  Previously assigned density values will be reviewed and adjusted if needed, after 
which the final clinical treatment plan will be created.   
 
5.5 
Quality Assurance of the Daily Treatment Plan 
 
Patient specific QA will be performed at each fraction prior to delivery of the treatment 
plan. Given that dose measurements will not be possible with the patient on the table, this 
will be achieved by performing an independent Monte Carlo dose calculation on the image 
of the day, using the exported beam parameters, and mapped electron density. The 
independently calculated dose distribution will be compared to the dose distribution 
exported from the MRgRT system, looking at dose volume histograms and 3D gamma 
analysis of all voxels within the patient. In addition, in-house plan integrity verification 
software will be utilized to evaluate plan quality and integrity via plan parameters including 
contours, beam angles, segments, and monitor units. After completion of the automated 
checks, a final review by physics will be required prior to proceeding to treatment delivery.  
 
5.6 
Follow Up 
 
Patients will be assessed once per week in routine on treatment visits to assess for acute 
toxicity. All patients will undergo routine clinical follow-up with no protocol-required 
follow-up studies after radiation therapy is complete.  
 
 

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6 
REGULATORY AND REPORTING REQUIREMENTS 
 
The entities providing oversight of safety and compliance with the protocol require reporting as 
outlined below. 
 
The Washington University Human Research Protection Office (HRPO) requires that all events 
meeting the definition of unanticipated problem or serious noncompliance be reported as outlined 
in Section 6.2. 
 
6.1 
Definitions 
 
 Adverse Events (AEs) 
 
Definition: any unfavorable medical occurrence in a human subject including any 
abnormal sign, symptom, or disease.  
 
Grading: the descriptions and grading scales found in the revised NCI Common 
Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for 
all toxicity reporting. A copy of the CTCAE version 5.0 can be downloaded from 
the CTEP website.  
 
Attribution (relatedness), Expectedness, and Seriousness: the definitions for the 
terms listed that should be used are those provided by the Department of Health 
and Human Services’ Office for Human Research Protections (OHRP). A copy of 
this guidance can be found on OHRP’s website:  
http://www.hhs.gov/ohrp/policy/advevntguid.html 
 
 Serious Adverse Event (SAE) 
 
Definition:  any adverse drug experience occurring at any dose that results in any 
of the following outcomes: 
o Death 
o A life-threatening adverse drug experience 
o Inpatient hospitalization or prolongation of existing hospitalization 
o A persistent or significant disability/incapacity (i.e., a substantial disruption 
of a person’s ability to conduct normal life functions) 
o A congenital anomaly/birth defect 
o Any other experience which, based upon appropriate medical judgment, 
may jeopardize the subject and may require medical or surgical intervention 
to prevent one of the outcomes listed above 
 
 Unexpected Adverse Experience  
 
Definition: any adverse drug experience, the specificity or severity of which is not 
consistent with the current investigator brochure (or risk information, if an IB is not 
required or available). 

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 Life-Threatening Adverse Experience 
 
Definition: any adverse drug experience that places the subject (in the view of the 
investigator) at immediate risk of death from the reaction as it occurred, i.e., it does 
not include a reaction that, had it occurred in a more severe form, might have caused 
death. 
 
 Unanticipated Problems 
 
Definition: 
  
• 
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;  
• 
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 a greater risk of harm 
(including physical, psychological, economic, or social harm) than was 
previously known or recognized.  
 
 Noncompliance 
 
Definition: failure to follow any applicable regulation or institutional policies that 
govern human subjects research or failure to follow the determinations of the IRB. 
Noncompliance may occur due to lack of knowledge or due to deliberate choice to 
ignore regulations, institutional policies, or determinations of the IRB 
 
 Serious Noncompliance 
 
Definition: noncompliance that materially increases risks, that results in substantial 
harm 
 
 Protocol Exceptions 
 
Definition: A planned deviation from the approved protocol that are under the 
research team’s control.  Exceptions apply only to a single participant or a singular 
situation.  
 
Pre-approval of all protocol exceptions must be obtained prior to the event. 
 

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6.2 
Reporting to the Human Research Protection Office (HRPO) at Washington 
University 
 
The PI is required to promptly notify the IRB of the following events:  
 
• 
Any unanticipated problems involving risks to participants or others which occur 
at WU, any BJH or SLCH institution, or that impacts participants or the conduct of 
the study.  
• 
Noncompliance with federal regulations or the requirements or determinations of 
the IRB.  
• 
Receipt of new information that may impact the willingness of participants to 
participate or continue participation in the research study.  
 
These events must be reported to the IRB within 10 working days of the occurrence of the 
event or notification to the PI of the event. The death of a research participant that qualifies 
as a reportable event should be reported within 1 working day of the occurrence of the 
event or notification to the PI of the event 
 
6.3 
Reporting to the Quality Assurance and Safety Monitoring Committee 
(QASMC) at Washington University  
 
The PI is required to notify the QASMC of any unanticipated problem occurring at WU 
or any BJH or SLCH institution that has been reported to and acknowledged by HRPO as 
reportable.  (Unanticipated problems reported to HRPO and withdrawn during the review 
process need not be reported to QASMC.) 
 
QASMC must be notified within 10 days of receipt of IRB acknowledgment via email to 
a QASMC auditor. 
 
6.4 
Timeframe for Reporting Required Events 
 
Adverse events captured in the CRFs will be tracked for 1 week following the last day of 
MRgRT. For the purposes of this protocol, reportable adverse events are toxicities that did 
not predate MRgRT and are probably or definitely attributable to protocol procedures. 
 
 
 

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7 
STUDY CALENDAR 
  
  
Screening 
MRI-guided 
Radiation Therapy 
Informed consent 
X  
  
Medical history 
 X 
  
MRI-Screening 
Questionnaire 
X 
 
Pregnancy test1 
 X 
  
Volumetric MRI 
 
X 
AE assessment 
 
X 
1. Women of childbearing potential only 
 
 
8 
DATA SUBMISSION SCHEDULE 
 
Case report forms with appropriate source documentation will be completed according to the 
schedule listed in this section. 
 
Case Report Form 
Submission Schedule 
Original Consent Form 
Prior to registration 
On-Study Form 
Prior to starting treatment 
Treatment Summary Form 
Completion of last fraction of MRgRT 
Toxicity Form 
Follow-up Form 
Continuously through 1 week after last treatment 
Death Form 
1 week after last treatment (if applicable) 
 
 
9 
DATA SAFETY AND MONITORING 
 
In compliance with the Washington University Institutional Data and Safety Monitoring Plan, the 
Principal Investigator will provide a Data and Safety Monitoring (DSM) report to the Washington 
University Quality Assurance and Safety Monitoring Committee (QASMC) semi-annually 
beginning six months after accrual has opened (if at least five patients have been enrolled) or one 
year after accrual has opened (if fewer than five patients have been enrolled at the six-month mark).  
The Principal Investigator will review all patient data at least every six months, and provide a 
semi-annual report to the QASMC. This report will include:  
 
• 
HRPO protocol number, protocol title, Principal Investigator name, data coordinator name, 
regulatory coordinator name, and statistician.  

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• 
Date of initial HRPO approval, date of most recent consent HRPO approval/revision, date 
of HRPO expiration, date of most recent QA audit, study status, and phase of study.  
• 
History of study including summary of substantive amendments; summary of accrual 
suspensions including start/stop dates and reason; and summary of protocol exceptions, 
error, or breach of confidentiality including start/stop dates and reason.  
• 
Study-wide target accrual and study-wide actual accrual.  
• 
Protocol activation date.  
• 
Average rate of accrual observed in year 1, year 2, and subsequent years  
• 
Expected accrual end date and accrual by cohort.  
• 
Objectives of protocol with supporting data and list the number of participants who have 
met each objective.  
• 
Measures of efficacy.  
• 
Early stopping rules with supporting data and list the number of participants who have met 
the early stopping rules.  
• 
Summary of toxicities separated by cohort with the number of dose-limiting toxicities 
indicated. 
• 
Abstract submissions/publications  
• 
Summary of any recent literature that may affect the safety or ethics of the study  
 
The study principal investigator and Research Patient Coordinator will monitor for serious 
toxicities on an ongoing basis. Once the principal investigator or Research Patient Coordinator 
becomes aware of an adverse event, the AE will be reported to the HRPO and QASMC according 
to institutional guidelines. 
  
 
10 
STATISTICAL CONSIDERATIONS 
 
10.1 
Sample Size Calculations 
 
Given this is a pilot study to demonstrate feasibility, clinical considerations instead of 
power calculations were used to determine sample size. The primary objective will be to 
report feasibility of same-session MRI-only simulation and treatment with MRI-guided 
palliative radiation therapy for painful metastasis, hemoptysis, GI bleeding, pelvic 
bleeding, and SVC syndrome/ bulky mediastinal disease. The goal accrual will be 20 
patients. We are interested in precise estimates of feasibility of the proposed treatment plan, 
as well as outcome variability that will aid in the planning of a larger, sufficiently powered 
efficacy trial.  A sample size of 20 will allow us to be relatively precise in our conclusions 
regarding feasibility outcomes.  For example, if we observe an 80% feasibility rate (i.e. 16 
patients out of the 20 enrolled in the study receiving at least 70% of their scheduled 
treatment fraction for each respective fraction), the 95% CI for that rate would be (62.5% 
- 97.5%).  Similarly, the secondary objectives do not require power calculations.  
 
10.2 
Stopping Criteria 
 
If at any point in trial enrollment, >2 out of the first 5 patients, or >4 out of the first 10 
patients are unable to complete the first fraction of treatment, the trial will be suspended. 

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If at any time a grade 5 toxicity (death) is observed that is probably or definitely attributable 
to treatment, accrual will be suspended and the event will be reviewed by the principal 
investigator. Since patients accruing to the trial have metastatic disease, it is anticipated 
that deaths unrelated to the trial may be observed. Death that is felt to be either due to 
disease progression or patient comorbidity will not be scored as grade 5 toxicity and will 
not result in trial suspension. 
 
10.3 
Statistical Analysis Plan 
 
Patient baseline characteristics will be presented as mean and standard deviation or count 
and percentage.  Overall feasibility will be reported as the number of patients receiving at 
least 70% of their scheduled treatment fraction for each respective fraction with percentage 
in all patients recruited, and a 95% confidence interval will be generated. Feasibility will 
be defined as 70% of patients receiving at least 70% of their scheduled treatment fraction.  
Second, fraction plans will be divided by median fraction used into two groups, low 
fraction group and high fraction group. Median feasibility and range will be described for 
each group, and a Wilcoxon rank-sum test will be used to compare the feasibility among 
the two different fraction groups. 
 
 
 
 
 

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11 
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Rodrigues G, Videtic GMM, Sur R, et al. Palliative thoracic radiotherapy in lung cancer: 
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Langendijk J a, ten Velde GP, Aaronson NK, de Jong JM, Muller MJ, Wouters EF. 
Quality of life after palliative radiotherapy in non-small cell lung cancer: a prospective 
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Tey J, Back MF, Shakespeare TP, et al. The role of palliative radiation therapy in 
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Biswal BM, Lal P, Rath GK, Mohanti BK. Hemostatic radiotherapy in carcinoma of the 
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Halle JS, Rosenman JG, Varia MA, Fowler WC, Walton LA, Currie JL. 1000 CGY single 
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