Radiopaque Hydrogel in Patients Undergoing Radiotherapy for Pancreatic Cancer
Condition: Pancreatic Adenocarcinoma
MeSH terms: Adenocarcinoma
Study type: Interventional

Summary: 
      The goal of this pilot imaging study is to evaluate the visibility of marking the interface
      between the pancreas and duodenum with TraceIT Tissue Marker. Patients with a pathologically
      confirmed diagnosis of BR/LAPC (borderline resectable/locally advanced pancreatic cancer)
      pancreatic adenocarcinomas indicated for neo-adjuvant image-guided radiotherapy with SBRT
      (stereotactic body radiation therapy) will be enrolled. This study will thus set the stage
      for further investigations using the TraceIT Tissue Marker to avoid duodenum toxicity with
      imaging localization, enabling further dose intensification with SBRT or IMRT to improve the
      clinical outcomes in BR/LAPC.
    

Detailed description: 
      Pancreatic ductal adenocarcinoma is now the third leading cause of cancer-related death, with
      a devastating 5-year overall survival (OS) rate of nearly 8%, despite having the 12th most
      common incidence of all malignancies in the United States. One-third of patients will present
      with borderline resectable or unresectable, locally advanced pancreatic cancer (BR/LAPC). In
      the cases of LAPC, chemotherapy with or without radiation may be recommended to improve the
      quality of life by relieving symptoms and extending survival. Despite aggressive combined
      modality therapy, the median survival remains between 9 and 15 months.

      Current guidelines for the management of BR/LAPC patients include single- or multi-agent
      chemotherapy or chemoradiation (CRT) in sequence with chemotherapy. Results of studies
      comparing chemotherapy alone to CRT for patients with BR/LAPC are mixed. The importance of
      local control or delaying local progression on improving morbidity and possibly mortality in
      patients with pancreatic cancer is supported by autopsy data demonstrating that 30% of
      patients die of locally destructive disease. It follows that in the cases of LAPC, advanced
      radiation therapy techniques using dose-escalation with intensity modulated radiotherapy
      (IMRT) and stereotactic body radiotherapy (SBRT) are potential strategies to improve local
      control.

      A consistent challenge to dose-escalation with IMRT (intensity modulation radiation therapy)
      or SBRT is the sensitivity of the surrounding gastrointestinal organs, particularly the small
      bowel which is directly adjacent to the head of the pancreas head of the pancreas (HOP). For
      BR/LAPC patients treated with CRT, advances in image guidance have provided the opportunity
      to safely deliver higher biologically effective doses of radiation therapy using IMRT of >70
      Gy (57.25 Gy in 25 fractions, BED 70.36 Gy) compared to standard fractionation regimens
      (50.40 Gy in 28 fractions or 50 Gy in 25 fractions, BED 59.47 Gy and 60 Gy, respectively).
      Those patients who underwent dose-escalated CRT with BED>70 Gy, did have a superior OS
      compared to those receiving BED<70 Gy, supporting the utility of dose-escalation in improving
      long-term outcomes. SBRT involves a short course of radiation therapy, five fractions or
      less, and has demonstrated higher rates of local control compared to CRT in other disease
      sites. Early studies evaluating SBRT for pancreatic cancer utilized single fractions of 25
      Gy, resulting in local control rates of 100% at 1 year but unacceptably high rates of
      gastrointestinal toxicity. More recently, hypofractionated SBRT (33 Gy total, 6.6 Gy daily
      fractions) has been evaluated and utilized by our group in an effort to reduce the toxicity
      of therapy, with results demonstrating nearly 80% rate of freedom from local progression at
      one year and an acceptable 11% long-term gastrointestinal toxicity. Outcomes with SBRT are
      thus promising; however, higher local control rates with dose-escalation may be achievable,
      but current practice is limited due to risks of toxicity.

      The goal of this pilot imaging study is to evaluate the visibility of marking the interface
      between the pancreas and duodenum with TraceIT Tissue Marker. Patients with a pathologically
      confirmed diagnosis of BR/LAPC pancreatic adenocarcinomas indicated for neo-adjuvant
      image-guided radiotherapy with SBRT will be enrolled. This study will thus set the stage for
      further investigations using the TraceIT Tissue Marker to avoid duodenum toxicity with
      imaging localization, enabling further dose intensification with SBRT or IMRT to improve the
      clinical outcomes in BR/LAPC.
    

Intervention name(s): TraceIT tissue marker injection
Intervention type(s): Device
Intervention description(s): The TraceIT injection will be performed during the endoscopic fiducial placement which is the standard of care. CTs to serially confirm TraceIT positioning will be performed on the same day during patient visits for their middle (2nd or 3rd fraction) and last (5th fraction) radiation therapy treatments.
Intervention model: Single Group Assignment
Intervention model description: marking the interface between the pancreas and duodenum with TraceIT Tissue Marker in patients undergoing image-guided radiotherapy
Masking: None (Open Label)
Primary purpose: Treatment