Comparison of Back-loaded vs Preloaded Fiducial Needles in EUS-guided Fiducial Marker Placement in Pancreatic Cancer.

Study Overview
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Brief Summary
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Endoscopic ultrasound (EUS) has been pivotal in accomplishing image guided radiation therapy (IGRT) in patients with pancreatic cancer by allowing precise contouring and identification of target lesions in the pancreas via placement of fiducials using fine needle aspiration (FNA) needles. Currently, back-loading the fiducials is the only option for preparing delivery of fiducials via the EUS approach. A prototype 22-Gauge EUS needle preloaded with four fiducials has recently been developed, and used in a porcine models with successful results. There are no randomized controlled trials comparing total duration of time needed for placement of fiducials using technical success of the traditional back- loading technique of fiducial markers to the new preloaded needles in regards to EUS based fiducial marker placement for IGRT in pancreatic cancer. Hypotheses Use of a 22 G preloaded needle for EUS guided fiducial marker placement in patients with pancreatic cancer will: Be delivered in at least require 60% less of the procedure time that it takes for traditional back-loaded 22G needles Improve overall procedure efficiency Maintain comparable technical success and adverse event rates. Primary Aims 1) To compare the procedure time of 22G needle placement of three Visicoil (brand of flexible linear back-loaded fiducial markers) fiducial markers and 22G needle preloaded fiducial markers. Secondary Aims To compare adverse event rates in 22G needle placement of Visicoil fiducial markers and 22G needle preloaded fiducial markers To compare endpoints of technical success defined as proper placement of two to three fiducial markers in a pancreatic neoplasm in 22G needle placement of Visicoil fiducial markers and 22G needle preloaded fiducial markers.

Detailed Description
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Pancreatic cancer is the twelfth most common cancer worldwide. Neoadjuvant chemoradiation therapy in patients with borderline resectable pancreatic adenocarcinoma has become standard of care and is associated with higher rates of complete resection ultimately with improvement of overall survival in this patient population. Radiation therapy to a soft tissue organ such as the pancreas can be difficult, as it is not readily visualized radiographically. Image guided radiation therapy (IGRT) is a commonly implemented modality for delivering high doses of radiation directed at cancer tissue, while reducing collateral damage to adjacent healthy tissue. Fiducials, which are inert radiographic markers typically made from gold or carbon, can be placed in and around the tumor to delineate tumor margins to allow for IGRT Endoscopic ultrasound (EUS) has been pivotal in accomplishing IGRT by allowing precise contouring and identification of target lesions in the pancreas via placement of fiducials. This has traditionally been accomplished with the use of 19-gauge or 22-gauge fine needle aspiration (FNA) needles. To prepare the needle for fiducial placement, one to two fiducials are manually back-loaded into the tip of the needle after the stylet has been removed. In order to hold the fiducials within the needle, sterile lubrication or bone wax can be applied. Once the pancreatic mass has been targeted, fiducial injection can be accomplished via stylet reinsertion or sterile water injection. Currently, back-loading the fiducials is the only option for preparing delivery of fiducials via the EUS approach. Difficulties associated with fiducial loading and deployment can increase procedure duration due to cumbersome fiducial back-loading, fiducial misplacement & migration, as well as inability to pass the fiducial marker through the needle due to endoscope angulation. Observational studies have sited a technical success rate of 86-100% using 19 and/or 22 gauge needles with average procedure time between 7-12 minutes using the fiducial back-loading technique. A new mode of fiducial delivery has recently been developed that hopes to circumvent some of the technical issues inherent to traditional fiducial marker loading and deployment. A prototype 22-Gauge EUS needle preloaded with four fiducials has been used in a porcine models with successful deployment 95.6% of the time all accurate on predetermined targets. They were deemed easy to pass, relatively easy to deploy, and easily visualized on EUS, with excellent fluoroscopic and CT visualization. In addition, time for deployment was on average less than 60 seconds. To date, there is no randomized controlled trials comparing total duration of time needed for placement of fiducials using technical success of the traditional back- loading technique of fiducial markers to the new preloaded needles in regards to EUS based fiducial marker placement for IGRT in pancreatic cancer. This will be a multicenter randomized controlled trial. Randomization be performed and patients will undergo Linear EUS and have fiducial marker placement via a traditional 22G back-loaded needle (Visicoil) or the new 22G preloaded needle (PreLoad4). Multiple endpoints will be recorded, including total length of procedure, how many markers are successfully deployed, and technical success (Ease of passage of delivery system, ease of deployment of fiducials, EUS visualization of delivery system needle, EUS visual appearance of fiducials, and time for fiducial placement defined as starting at time of removing the needle from its packaging and ending time as removal of needle after final marker deployment). Fiducial marker location will be confirmed via fluoroscopy at time of placement and on 4D treatment planning CT ordered by the radiation oncologist for simulation. Patients will be discharged home after post procedure recovery. Patients will be contacted at home by a research coordinator or endoscopy staff 24-48 hours and 7-10 days after the procedure to document any immediate and delayed complications. Patients will return for their IGRT visit, and any evidence of fiducial marker migration will be recorded by the radiation oncologist. Hypotheses Use of a 22 G preloaded needle for EUS guided fiducial marker placement in patients with pancreatic cancer will: Be delivered in at least require 60% less of the procedure time that it takes for traditional back-loaded 22G needles Improve overall procedure efficiency Maintain comparable technical success and adverse event rates. Primary Aims 1) To compare the procedure time of 22G needle placement of three Visicoil fiducial markers and 22G needle preloaded fiducial markers. Secondary Aims To compare adverse event rates in 22G needle placement of Visicoil fiducial markers and 22G needle preloaded fiducial markers To compare endpoints of technical success defined as proper placement of two to three fiducial markers in a pancreatic neoplasm in 22G needle placement of Visicoil fiducial markers and 22G needle preloaded fiducial markers.

Official Title
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Comparison of Traditional Back-loaded Fiducial Needles With Preloaded Fiducial Needles in EUS-guided Fiducial Marker Placement for Image-guided Radiation Therapy in Patients With Pancreatic Cancer: A Multicenter Randomized Controlled Trial.

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Device: Back-loaded Needle (Device)
* Device: Preloaded Needle (Device)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Patients with pathologically confirmed pancreatic cancer referred for image guided radiation therapy (IGRT) Exclusion Criteria: Age <18 Inability to consent Known coagulopathy/thrombocytopenia (INR >1.5, platelets <75) Patients on antiplatelet/anticoagulant medication that cannot safely be discontinued 5-7 days prior to the procedure Gold allergy Current infection EUS evidence of vessel interfering with path of fiducial marker Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Back-loaded needle<br>The patients will undergo Linear EUS and have fiducial marker placement via a traditional 22G back-loaded needle. CRFs will be used to record data for primary and secondary endpoints. | Device: Back-loaded Needle (Device)<br>* Fiducial marker placement via a traditional 22G back-loaded needle will be performed with multiple endpoints recorded: total length of procedure how many markers are successfully deployed technical success Fiducial marker location will be confirmed via fluoroscopy at time of placement and on 4D treatment planning CT ordered by the radiation oncologist for simulation.<br>|
| Experimental: Preloaded Needle<br>The patients will undergo Linear EUS and have fiducial marker placement via a traditional 22G preloaded needle. CRFs will be used to record data for primary and secondary endpoints. | Device: Preloaded Needle (Device)<br>* Fiducial marker placement via a novel 22G preloaded needle will be performed with multiple endpoints recorded: total length of procedure how many markers are successfully deployed technical success Fiducial marker location will be confirmed via fluoroscopy at time of placement and on 4D treatment planning CT ordered by the radiation oncologist for simulation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Procedure Duration Required for Placing the Fiducial Markers | Duration of procedure for placing fiducial markers including: Fiducial package was opened start time (start stop watch) + Fiducial placement end time (end stop watch) = Placing Fiducial Markers Time | During scheduled procedure (approximately 1 hour) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Procedure Time | Total procedure time will be recorded during the procedure using a case report form (CRF) for Procedure Time | During scheduled procedure (approximately 1 hour) | 
| Number of Participants With Technical Success EUS Needle Visualization | EUS needle visualization during the procedure will be recorded on a CRF for Scale of Technical Success. | During scheduled procedure (approximately 1 hour) | 
| Technical Success | Defined as the proper placement of 3 fiducial markers in a pancreatic neoplasm in 2 different planes | During scheduled procedure (approximately 1 hour) | 
| Number of Participants With Visualization of Fiducials as Assessed by Radiation Oncology | Fiducial location on CT scan will be assessed at patient's radiation oncology appointments for IGRT. | Several hours to 7 days after fiducial marker deployment | 
| Number of Participants With Inadvertent Deployment of Fiducials | Whether inadvertent deployment of fiducials occurs will be recorded on a CRF for Data Acquisition | During scheduled procedure (approximately 1 hour) | 
| Number of Participants With Ease of Passage of Delivery System | Ease of needle device passage through EUS will be recorded on a CRF form for technical success. | During scheduled procedure (approximately 1 hour) | 
| Number of Fiducials Placed | Number of fiducials placed will be recorded during the procedure using a case report form (CRF) for Fiducial Placement Data | During scheduled procedure (about 90 minutes) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pancreatic cancer, Image guided radiation therapy, Fiducial marker placement, Endoscopic ultrasound