Comparison Study in Pancreatic Fiducial Placement
Phase: NA
Conditions: Pancreatic Neoplasms
Sponsor: Parkview Health

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PRC14-1020 Pancreatic Fiducial 
Parkview Regional Medical Cancer and Parkview Research Center 
Comparison Study between 19 gauge EUS FNA BNX Needle vs. 22 gauge EUS FNA BNX 
Needle in Pancreatic Fiducial Placement to Treat Pancreatic Cancer 
 
 
Principal Investigator (PI) 
Neil Sharma, MD 
Physician Executive/Service Line Physician Leader for Cancer Service Line 
Parkview Regional Medical Center 
11104 Parkview Circle Drive, Suite 310 
Fort Wayne, IN 46845 
e-mail: nrsharma219@yahoo.com 
 
 
Primary Coordinator 
Breck Hunnicutt, RN, BSN, CCRC 
Parkview Research Center 
3602 New Vision Drive 
Fort Wayne, IN 46845 
e-mail breck.hunnicutt@parkview.com 
Phone number: 260-266-9168 
Fax number: 260-266-9169 
 
 
Regulatory Coordinator 
Judy Irvin, RN, CCRC 
Parkview Research Center 
3602 New Vision Drive 
Fort Wayne, IN 46845 
e-mail Judith.irvin@parkview.com 
Phone number: 260-266-5612 
Fax number: 260-266-5656 
 
 
Statistician  
Christopher Bradley, PhD 
e-mail Christopher@3rsr.com 
Phone number: 260-267-8958 
 
 
 
 
 
 

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Contents 
1.0 Purpose ............................................................................................................................... 4 
2.0 Background .......................................................................................................................... 4 
3.0 Study Objectives .................................................................................................................. 5 
3.1 Primary Objectives ........................................................................................................... 5 
3.2 Secondary Objectives ....................................................................................................... 5 
4.0 Study Design ........................................................................................................................ 5 
5.0 Selection of Patients ............................................................................................................ 7 
6.0 Inclusion ............................................................................................................................... 7 
7.0 Exclusion ............................................................................................................................. 7 
8.0 Subject Confidentiality and HIPAA Compliance .................................................................... 7 
9.0 Randomization ..................................................................................................................... 8 
10. Information Required ............................................................................................................ 8 
10.1 Prior to fiducial placement .............................................................................................. 8 
10.2 During Fiducial Placement .............................................................................................. 8 
10.3 Post Fiducial Placement ................................................................................................. 9 
10.4  Complications during/After the procedure ...................................................................... 9 
10.5 Migration of fiducials ....................................................................................................... 9 
10.6 Ability to receive SBRT ................................................................................................... 9 
11.0   Adverse Event Reporting ................................................................................................10 
11.1 Adverse events will be collected at the following time points ..........................................10 
12.0 Serious Adverse Event (SAE) Reporting ...........................................................................10 
12.1 Definition of an SAE.......................................................................................................10 
13.0 Data and Safety Monitoring ...............................................................................................10 
14.0 Sample Size ......................................................................................................................10 
15.0 Statistical Analysis Plan ....................................................................................................11 
15.1 Primary Endpoints .........................................................................................................11 

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15.2 Secondary Endpoints .....................................................................................................11 
15.3 Enrollment .....................................................................................................................11 
15.4 Study Hypothesis ...........................................................................................................11 
15.5 Interim Analysis .............................................................................................................11 
16.0 Subject Withdrawal ...........................................................................................................12 
17.0 Data Collection and Management .....................................................................................12 
18.0 Responsibility of Principal Investigator ..............................................................................12 
19.0 Responsibility of Study Site ...............................................................................................12 
20.0 Conduct of Study ...............................................................................................................13 
20.1 Ethical Conduct of the Study ..........................................................................................13 
20.2 Informed Consent ..........................................................................................................13 
    20.3 Institutional Review Board/Ethics Committee;;;;;;;;;;;;;;;;...;. 13 
21.0 List of References;;;;;;;;;;;;;;;;;;;;;;;;;;;;;...; 14 
Appendix A Optional Tool – Check List;;;;;;;;;;;;;;;;;;;;;;;; 15 
Appendix B Optional Tool – CRF Completion Guidelines;;;;;;;;;;;;;;;;. 16 
 
 
 
 
 
 
 
 
 
 
 

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1.0 Purpose 
The primary purpose of this prospective multicenter study is to compare the cost, time, 
complications, and migration rate of two FDA approved needles; 19 gauge endoscopic 
ultrasound (EUS) fine needle aspiration (FNA) BNX needles to 22 gauge EUS FNA BNX 
needles.  
2.0 Background 
Pancreatic cancer is among the most deadly cancers in the United Sates.  It is the ninth 
and tenth most common cancers among women and men respectively.  Approximately 
forty-five thousand people were diagnosed with pancreatic cancer in 2013 in the United 
States.  Only six percent of people with pancreatic cancer are expected to survive five 
years and it is responsible for seven percent of all cancer deaths.1   
 
Treatment of non-resectable pancreatic cancer includes stereotactic radiotherapy which 
delivery methods include CyberKnife and Tomotherapy.2, 3  The Cyberknife radiotherapy 
system and Tomotherapy radiotherapy system delivers noninvasive image-guided 
frameless radiosurgery, that is considered to be an alternative to conventional surgery.2  
Both delivery methods utilize the insertion of fiducial markers to facilitate accurate 
delivery of dose intensified radiotherapy. 3 This method of delivery relies on Image 
Guided Radiation Therapy (IGRT) to enable the delivery of a high dose radiation while 
having minimal effects on surrounding tissue, resulting in less adverse events by gating 
the respiratory motion and accommodating the tumor movement.4  The fiducial markers 
are essential to ensure that there is interfractional certainty.5 
 
Traditionally, percutaneous insertion of fiducial markers utilizing Computerized 
Tomography (CT) guided placement or surgery has been used to facilitate the delivery of 
stereotactic radiotherapy.6  EUS-guided fiducial marker placement has been introduced 
as a safe and feasible alternate method to CT guided placement.7, 8  Sanders et al., in a 
prospective study involving fifty-one patients evaluating safety, feasibility, and the ability 
to receive Stereotactic Body Radiation Therapy (SBRT) with EUS-guided marker 
placement using a nineteen gauge needle, found that fiducial placement was achieved in 
ninety percent of the cases with spontaneous migration found in seven percent of the 
cases requiring a second EUS-guided fiducial marker placement.  Ninety-one percent of 
the patients successfully received SBRT, concluding that EUS-guide marker placement 
is safe and feasible for SBRT treatment of locally advanced pancreatic cancer.9  
 
Both 19 gauge and 22 gauge needles are used to insert the markers per EUS-guided 
method.  Ammar et al., noted that a 22 gauge needle may permit greater access, and 
also noted, that the need for a comparison trial of the two needles would be beneficial.10    
Khashab et al., compared the traditional fiducial marker to the coiled marker which 
differed in size. The use of a 19 gauge needle and a 22 gauge needle were utilized to 
accommodate the fiducial marker size.  They noted the ideal needle characteristics 

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PRC14-1020 Pancreatic Fiducial 
include the ability to incorporate multiple fiducial markers, good visibility, and ease of 
fiducial deployment.11   
 
The intent of this study is to compare two commercially available needles, 19 gauge 
EUS FNA BNX needles vs. 22 gauge EUS FNA BNX needles in EUS-guided fiducial 
marker placement to treat patients with locally advanced pancreatic cancer who are not 
undergoing resection.  Comparison of cost, time, complications, migration and the ability 
to receive SBRT will be evaluated. 
   
3.0 Study Objectives 
3.1 Primary Objectives 
3.1.1  Determine the difference in cost between the utilization of using 19 gauge 
EUS FNA BNX needles to 22 gauge EUS FNA BNX needles for fiducial 
placement. 
3.1.2  Determine the difference in the amount of time required to place 
pancreatic fiducials for pancreatic cancer between 19 gauge EUS FNA 
BNX needles to 22 gauge EUS FNA BNX needles. 
 
3.2 Secondary Objectives 
3.2.1  Determine the difference in rate of migration between 19 gauge EUS FNA 
BNX needles to 22 gauge EUS FNA BNX needles in patients in whom 
fiducial placement was performed. 
3.2.2 Determine the difference in rate of post-procedure complications between 
19 gauge EUS FNA BNX needles to 22 gauge EUS FNA BNX needles. 
 
4.0 Study Design 
This is a randomized prospective multicenter trial.  A minimum of 14 patients and a 
maximum of 30 patients will be enrolled at up to ten participating sites.  Enrollment is 
projected to be complete when enough data has been collected for statistical analysis.   
 
Participating sites will consist of tertiary referral centers (either academic or community).  
The participating physicians are required to have experience as advanced interventional 
expert endoscopists as demonstrated by prior experience with endoscopic ultrasound 
based procedures involving the pancreas and prior experience of performing a minimum 
of five EUS guided fiducial marker placements in the pancreas. A Parkview Research 
Center (PRC) review committee will need to validate and approve the Principal 
Investigator before he/she may participate in this study. PRC will send a status letter of 
approval to the physician. 
 
Adult subjects with a diagnosis of pancreatic cancer who will receive SBRT for 
pancreatic cancer via Cyberknife or Tomotherapy will undergo EUS guided fiducial 

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marker placement.  The study duration will commence at the time of EUS guided fiducial 
marker placement and conclude at the time of last SBRT to the pancreas. 
 
Subjects will be randomized to receive fiducial marker placement with either a 19 gauge 
EUS, FNA BNX needle or a 22 gauge EUS, FNA BNX needle.  A single sheath and a 
single needle 19 gauge EUS, FNA, BNX needle using a Visicoil twin line with spacers 
will be utilized and a total of four fiducials (2 twin lines) will be placed in ARM 1.  A single 
sheath and a total of four 22 gauge EUS, FNA, BNX needles will be used to place a total 
of four fiducials in ARM 2. Fiducial size will be per institutional standards. For all 
patients, standard hospital protocol will be followed for EUS procedures and patient care 
management. 
 
Cost effectiveness will be evaluated by providing an itemized statement, including 
anesthesiologist, and endoscopist charges.  Time in both arms starts when the first 
needle is loaded and sealed with bone wax.  The patient is under anesthesia, in position, 
and staff is ready for the case. The time ends when last fiducial is placed.  When using a 
22 gauge needle, assistance to load blank needles is allowed if desired. Complications 
will be reported and may include but not limited to pain, bleeding, peritonitis, and 
pancreatitis.  Migration will be reported during the timeframe from simulation to the last 
day of SBRT.  The ability to receive SBRT from this EUS guided fiducial placement will 
be reported as simply a yes or no.   Sites will provide a de-identified itemized statement 
for EUS guided fiducial placement procedure, prior to any discounted rate, including the 
endoscopist and anesthesiologist. 
 
Follow up evaluations and treatment for pancreatic cancer will be performed in 
accordance with standard of care procedures and procedures deemed necessary by the 
attending physician.  
 
Computerized Tomography Simulation (CT SIM) and set up will be performed per 
institutional policy and procedure.  
 
There will be fiducials placed in the pancreas according to facility policy and procedure.  
 
The participating site will obtain appropriate Institutional Review Board (IRB) approval 
prior to participating in any research activities.  The participating site will provide PRC 
with a copy of their IRB approval prior to any study procedures. PRC will also need to 
collect the participating sites’ IRB of records IRB registration and FWA to confirm 
compliance. 
 
Once IRB approval has been confirmed by the coordinating site, the participating site will 
receive enrollment instructions, case report forms and the randomly assigned sealed 
envelopes.  
 

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5.0 Selection of Subjects 
This study will include patients with pancreatic cancer who will receive fiducial marker 
placement in order to receive Cyberknife treatment to the pancreas. 
 
6.0 Inclusion 
6.1      Subjects that plan to undergo CyberKnife treatment for pancreatic cancer 
6.2      Subjects that are deemed physically able to undergo anesthesia (either Monitored    
           Anesthesia Care (MAC) or general anesthesia) 
6.3   Subjects (or the subjects Legally Authorized Representative [LAR]) that have 
agreed to participate in the study and have signed Informed Consent 
  
6.4  
Subjects 18 years of age or older 
6.5  
Subject must be able to hold anticoagulants as per institutional standard of care  
6.6 
Women of child bearing potential who are not pregnant as proven by a negative   
pregnancy test 
 
7.0 Exclusion 
7.1  
Subjects that are unable to tolerate anesthesia for the procedure 
7.2  
Subjects 17 or under 
7.3  
Subjects that refuse treatment for pancreatic cancer 
7.4  
Subjects whose anticoagulants cannot be held  
7.5  
Subjects who have distant metastatic disease 
7.6  
Subjects who cannot or refuse EUS guided procedures.   
7.7 
Subjects who are pregnant  
 
8.0 Subject Confidentiality and HIPAA Compliance 
To ensure that the confidentiality of subjects’ identification is maintained and medical 
records are protected, subject names will not be used in the study.  A unique subject 
identifier will be assigned to each subject enrolled in the study.  Each participating site 
will maintain a list that cross-references subjects’ identification.  The participating site will 
control their own subject’s identity.  To ensure that subjects’ identification and medical 
records are protected, the list will be kept confidential and only accessible to the PI, 
his/her staff, and the appropriate research representative responsible for ensuring the 
quality of the reported data.  Subject’s records may be reviewed by research 
representative to verify the quality of the reported data; however, confidentiality will be 
maintained.   
 
Subjects will provide the appropriate authorization to allow the use and disclosure of 
their personal health records in accordance with the applicable laws and regulations 
including, but not limited to, HIPAA requirements. 
 

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9.0 Randomization 
Subjects receiving EUS and fluoroscopic guidance for placement of fiducial markers into 
the pancreas will be randomized into two groups in a balanced manner to either the 19 
gauge technique (ARM 1) or the 22 gauge technique (ARM 2) of EUS guided fiducial 
marker technique according to a predetermined computer generated randomization. 
 
When the procedure has been scheduled the site should email the coordinating site at 
oncology.research@parkview.com for your randomization instructions. 
Two sealed envelopes will be appended to each subjects folder they will be marked A 
and B.  A sheet of paper inside the envelopes will indicate either “19” indicating 19 
gauge technique (Treatment ARM 1) or “22” indicating 22 gauge technique (Treatment 
ARM 2). 
The envelope will only be opened during the procedure after the endoscopy has been 
initiated. 
 
10. Information Required 
10.1  Prior to fiducial placement 
10.1.1   Eligibility Checklist 
10.1.2  Obtain Informed Consent 
10.1.3  Patient information 
 
Gender 
 
Date of Birth 
 
Height 
 
Weight 
10.1.4  Comorbidities 
 
Smoker 
 
Diabetes (type I or type II) 
 
Chronic Lung Disease 
 
Cardiac Disease 
 
Pancreatitis 
 
Hepatitis 
 
Hypertension 
 
Anticoagulation Status 
10.1.5  Disease Characteristics 
 
Recurrent 
 
Stage 
 
Pathology 
 
Diagnostic Testing 
10.1.6  History of chemotherapy and radiation  
 
    
10.2 During Fiducial Placement 

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10.2.1 Time measurement  
 
Time in both arms starts when the first needle is loaded and sealed 
with bone wax.  The patient is under anesthesia, in position, and staff 
is ready for the case. The time ends when last fiducial is 
placed.  When using a 22 gauge needle, assistance to load blank 
needles is allowed if desired. 
10.2.2   Needle type used 
10.2.3  Number fiducials placed 
10.2.4   Size of fiducials placed 
10.2.5   Type of fiducials placed 
 
10.3 Post Fiducial Placement 
10.3.1 Cost  
 
Itemized charges to patient for procedure including anesthesiologist 
and endoscopist prior to any discounted rate. 
10.4 Complications during/after the procedure: 
10.4.1  Admission for pain 
10.4.2   Need for laparoscopic or open surgery 
10.4.3   Any additional endoscopic procedures to control bleeding 
10.4.4   Peritonitis 
10.4.5  Need for transfusion 
10.4.6   Requiring hospital admission or emergency room visit 
10.4.7   Pancreatitis 
 
10.5 Migration of fiducials 
10.5.1  Observation of fiducial migration from time of treatment planning to the 
last SBRT. 
 
  
10.6 Ability to receive SBRT  
10.6.1  Yes or No 
 
10.7 Transmission of Case Report Forms (CRF) and other pertinent study material 
 
 
 
10.7.1  Scanning 
 
 
 
10.7.1.1 Scan to breck.hunnicutt@parkview.com 
 
 
10.7.2  Faxing 
 
 
 
10.7.2.1 Fax to 260-266-9169 c/o Breck Hunnicutt 
10.8 Queries 
 
 
 
10.8.1  All queries will be communicated through email 
 
 
10.8.2  Query response is requested with two weeks of receipt  

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11.0   Adverse Event Reporting 
11.1 Adverse events will be collected at the following time points: 
• 
Baseline 
• 
Completion of procedure, prior to discharge 
• 
72 hours post procedure 
• 
Last day of SBRT treatment 
• 
Migration of fiducial markers at any time prior to completion of SBRT treatment 
will be reported. 
 
12.0 Serious Adverse Event (SAE) Reporting 
All serious adverse events will be reported to Neil Sharma, M.D. by way of Breck 
Hunnicutt within 24 hours by calling 260-266-9168.  This call should be followed by the 
SAE CRF submission within 10 days by faxing the submission to Breck at 260-266-9169 
or email her at breck.hunnicutt@parkview.com 
A monitoring board lead by Dr. Sharma will review all incoming SAE’s. 
 
         12.1 Definition of an SAE: Any adverse event that results in any of the following  
        outcomes: 
 
• 
Death; 
• 
A life-threatening adverse experience; 
• 
Inpatient hospitalization or prolongation of existing hospitalization; 
• 
A persistent or significant disability/incapacity; 
• 
Important medical events that may not result in death, be life threatening, or 
require hospitalization may be considered an SAE, when, based upon medical 
judgment, they may jeopardize the patient and may require medical or surgical 
intervention to prevent one of the outcomes listed in the definition 
13.0 Data and Safety Monitoring 
It is the responsibility of the Principal Investigator to oversee the safety of the study at 
his/her site.  This safety monitoring will include careful assessment and appropriate 
reporting of adverse events as noted above.  Medical monitoring will include a quarterly 
assessment of the number and type of serious adverse events.  
14.0 Sample Size 
A minimum of 14 subjects and a maximum of 30 subjects are expected to be enrolled. 
Approximately one half of the subjects receiving fiducial markers via 19 gauge EUS FNA 
needle and approximately one half of the subjects receiving fiducial markers via 22 
gauge EUS FNA needle. The relatively small sample size will require the use of a non-
parametric statistical test.  Further, the detection of statistically significant results may be 

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difficult to detect due to the small sample size. 12 As such, the alpha level for all tests 
may be relaxed to the .10 level if significant effects are not detected at the .05 level.  
15.0 Statistical Analysis Plan 
15.1 Primary Endpoints 
• 
The primary endpoint for this study is total cost and time of EUS guided fiducial 
placement in the pancreas to facilitate SBRT treatment of pancreatic cancer. 
 
15.2 Secondary Endpoints 
• 
The secondary endpoints for this study are the migration rate of fiducials 
between placement and SBRT treatment to the pancreas and the rate of 
immediate complications after placement of fiducials. 
 
15.3 Enrollment  
• 
Approximately 14 subjects and a maximum of 30 subjects are expected to be 
enrolled. With approximately one half of the subjects randomized to ARM 1 (19 
Gauge EUS FNA needle technique) and approximately one half of the subjects 
randomized to ARM 2 (22 gauge EUS FNA needle technique). 
 
15.4 Study Hypothesis 
• 
This study is designed to test the null hypothesis that the 19 gauge EUS FNA 
BNX needles will have no variances related to cost, time, complication rate and 
migration rate to the 22 gauge EUS FNA BNX needles. 
H0 :  G19 = G22 
H1 : G19  =/  G22 
 
G19= 19 gauge EUS FNA BNX Needles 
G22= 22 gauge EUS FNA BNX Needles 
 
15.5 Interim Analysis 
• 
Given that only a minimum of 14 subjects will be enrolled, a non-parametric 
statistical analysis technique is required.12 Four separate areas will be examined: 
(1) cost; (2) time; (3) rate of migration, and; (4) complications.  In all areas, the 
independent variable is a dichotomous nominal level indictor that identifies 
whether patients are enrolled in ARM 1 or ARM 2.  The dependent variables of 
time, cost and migration are continuous markers of the concepts in 
question.  Under normal circumstances, the use of an independent samples t-test 
is appropriate when the dependent variable is continuous in nature and the 
independent variable is a dichotomous nominal-level variable.13  Under the 
current analysis scenario, the non-parametric equivalent of the t-test, which is the 
Wilcoxon-Mann-Whitney test,12 is appropriate. 

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The dependent variable that will estimate the presence of immediate complications and 
complications after the surgery will be reduced to a series of dichotomous indicators that 
will indicate the presence of admission for pain, the need for laparoscopic or open 
surgery, any additional endoscopic procedures to control bleeding, peritonitis, the need 
for transfusion, pancreatitis, or the need for a hospital admission or an emergency room 
visit.  These seven dependent variables will be juxtaposed against the independent 
variable that identifies whether a patient is enrolled in ARM1 or ARM2 through a series 
of cross tabulations.  The Chi-Square statistic13, 12 will then be used to determine if 
statistically significant differences in each of the seven dependent variables exists as a 
function of the independent variable. 
16.0 Subject Withdrawal 
A subject has the right to withdraw from the study at any time for any reason without 
prejudice to their future medical care by the physician or the institution.  The investigator 
and sponsor also have the right to withdraw subjects from the study in the event of 
comorbidities, adverse events, treatment failure, protocol deviation, or other reasons.  
Should a subject (or subject’s legally authorized guardian/representative) decide to 
withdraw; all efforts will be made to complete and report the observations as thoroughly 
as possible. 
17.0 Data Collection and Management 
For each subject for which informed consent has been obtained, a CRF must be 
completed by the PI or by their designee and signed by the PI, to certify that the data 
within each CRF is complete and correct.  Every effort should be made to respond to all 
questions on each CRF page. All CRF’s should be completed to identify the physician, 
subject number, and subject initials.  At no time should the subjects name appear in the 
CRF. Every effort should be taken to protect the subject health information.  Complete 
data is required in order to provide statistical analysis for each subject.  All CRF’s should 
be submitted to the coordinating site within 4 weeks. 
18.0 Responsibility of Principal Investigator 
 
• 
Conduct the study in accordance with the relevant, current protocol. 
• 
Personally conduct or supervise the described investigation. 
• 
Analysis of Complications and Adverse Events with respect to their clinical 
relevance and cause relation. 
• 
Evaluation of necessary protocol amendments. 
• 
Ensure that all associates, colleagues and employees assisting in the conduct of 
the study are informed about their obligations. 
• 
Agree to maintain adequate and accurate records and to make those records 
available for inspection in accordance with regulations. 
 
19.0 Responsibility of Participating Site 
• 
The site will consist of the Principal Investigators and his/her research team.  

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• 
Each Investigator within the participating site is responsible to conduct the Study in 
full compliance with the protocol and assure that data collection is complete and 
accurate. 
 
20.0 Conduct of Study 
20.1 Ethical Conduct of the Study  
This study will be conducted in accordance with applicable local, state, national 
laws and requirements. 
 
20.2 Informed Consent 
Informed Consent will be obtained from each subject and must be appropriately 
signed and dated.  It is the PI or PI’s designee’s responsibility to obtain written 
informed consent from the subject or subject’s legally authorized guardian prior 
to any protocol specific screening procedures being done.   All subjects in this 
study should be completely informed about the purpose, risks, benefits, and 
other pertinent details of this study.  The original signed copies of consent forms 
will be maintained by the participating site.  
 
Subjects will provide the appropriate authorization to allow the use and 
disclosure of their Protected Health Information (PHI) in accordance with 
applicable laws and regulations, including but not limited to, HIPAA requirements. 
 
20.3 Institutional Review Board/Ethics Committee 
Written approval of the protocol must be obtained prior to subject enrollment.  A 
copy of the letter indicating IRB approval must be provided to the sponsor.  
Annual updates must be submitted to the IRB by the PI for studies longer than 
one year or as dictated by the participating sites IRB.  Serious or unanticipated 
adverse events occurring during the study must also be submitted as per the 
Institution’s IRB policy.   
 
SIGNATURE LINE 
 
My name type below shall have the same force and effect and is as legally binding as 
my written signature. 
 
_Neil Sharma, MD                                    
 
___April 27, 2015______ 
Principal Investigator 
 
 
 
 
 
 
Date 
 
 
 

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List of References 
 
1. American Cancer Society. Cancer Facts & Figures 2013 Atlanta: American Cancer 
Society; 2013. 
2. Chang, S., Main, W., Martin, D., et al. An analysis of the accuracy of the CyberKnife: 
a robotic frameless stereotactic radiosurgical system. Neurosurgery. 2003 
Jan;52(1):140-6; discussion 146-7. 
3. Moseley, D., White, E., Whiltshire, K., et al.  Comparison of localization performance 
with implanted fiducial markers and cone-beam computed tomography for on-line 
image-guided radiotherapy of the prostate. International Journal of Radiation 
Oncology*Biology*Physics. 2007 March;67(3): 942-953. 
4. Chang, D., Schellenberg, D., Schen, J., et al. Stereotactic radiotherapy for 
unresectable adenocarcinoma of the pancreas.  Cancer. 2009 Feb;115(3): 665-672.  
5. Jayachandran, P., Minn, Y., Van Dam, J., et al. Interfractional Uncertainty in the 
Treatment of Pancreatic Cancer With Radiation. International Journal of Radiation 
Oncology*Biology*Physics. 2010 Feb;76(2): 603-7.  
6. Sotiropoulou E., Stathochristopoulou, I., Stathopoulos, K., et al. CT-Guided Fiducial 
Placement for CyberKnife Stereotactic Radiosurgery: An Initial Experience. 
CardioVascular and Interventional Radiology. 2010 June;33(3): 586-9. 
7. Park, W., Yan, B., Schellenberg, D., et al., EUS-guided gold fiducial insertion for 
image-guided radiation therapy of pancreatic cancer: 50 successful cases without 
fluoroscopy. Gastrointestinal Endoscopy. 2010 March;71(3): 513-18. 
8. Kim, J., Hong, S., Kim, J., et al. Safety and Efficacy of Ultrasound-Guided Fiducial 
Marker Implantation for CyberKnife Radiation Therapy. Korean Journal Radiology. 
2012 May-Jun; 13(3): 307–313.   
9. Sanders, M., Moser, A., Khalid, A., et al. EUS-guided fiducial placement for 
stereotactic body radiotherapy in locally advanced and recurrent pancreatic cancer. 
Gastrointestinal Endoscopy. 2010 June;71(7): 1178-84. 
10. Ammar, T., Coté, G., Creach, K., et al. Fiducial placement for stereotactic radiation 
by using EUS: feasibility when using a marker compatible with a standard 22-gauge 
needle. Gastrointestinal Endoscopy. 2010 71(3) 630-3. 
11. Khashab, M., Kim, K., Tryggestad, E., et al. Comparative analysis of traditional and 
coiled fiducials implanted during EUS for pancreatic cancer patients receiving 
stereotactic body radiation therapy. Gastrointestinal Endoscopy. 2012 Nov;76(5): 
962–971. 
12. Sprent, P.  (1989).  Applied Nonparametric Statistical Methods, Second 
Edition.  Boca Raton,   FL: Chapman & Hall 
13. Ritchey, F.  (2008).  The Statistical Imagination: Elementary Statistics for the Social 
Sciences, Second Edition.  Boston, MA: McGraw-Hill. 
 
 
 
 
 

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Appendix A 
Optional Tool - Check List 
Check List to be done in this order 
1. Patient Scheduled for Pancreatic Fiducial Placement
    due to Pancreatic Cancer 
 
2. Patient meets Inclusion/Exclusion Criteria
 
3. Informed Consent Obtained
 
4. Eligibility Checklist Completed
 
5. Email Coordinating Center for Randomization 
    Provide:  Institution Name 
                    Date of Procedure 
                    Patient Initials 
 
6. Randomization Email from Coordinating Center
    Information provided from them: 
                    Subject ID 
                    Randomization Code (Envelope A or B) 
 
 
 
 
 
 
 

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Appendix B 
Optional Tool - CRF Completion Guidelines 
Case Report 
Form 
Prior to 
Fiducial 
Placement 
or Baseline 
During
Fiducial 
Placement 
Completion of 
procedure, 
prior to 
discharge 
72 hours port 
procedure 
Last day of 
SBRT treatment
Migration of 
Fiducial marker 
(if needed 
Eligibility
Checklist 
 
X
Subject 
Demographics 
 
X
Fiducial 
Placement 
 
X
Adverse Events
 
X
X
X
X
X
*Serious 
Adverse Events
 
X
X
X
X
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*All Serious Adverse Events to be reported to Dr. Sharma by way of Breck Hunnicutt within 24 hours by calling 260-266-9168.  This should be 
followed by the SAE CRF submission within 10 days by faxing the submission to 260-266-9169