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

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:

1. Be delivered in at least require 60% less of the procedure time that it takes for
traditional back-loaded 22G needles

2. Improve overall procedure efficiency

3. 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

1. To compare adverse event rates in 22G needle placement of Visicoil fiducial markers and
22G needle preloaded fiducial markers

2. 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.

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