Endoscopic Ultrasound-guided RadioFrequency Ablation for the Treatment Pancreatic NeuroEndocrine Neoplasms

Study Overview
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Brief Summary
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This study evaluates the possibility and the safety of performing local therapy for Pancreatic neuroendocrine neoplasms (PanNENs) using radiofrequency ablation of the tumor under ultrasonography (EUS) guidance.

Detailed Description
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Pancreatic neuroendocrine neoplasms (PanNENs) are rare, but their incidence has significantly increased in the last decades. The mainstay treatment of PanNENs is surgery, which is associated with a significant benefit in term of survival but also with significant short- and long-term adverse events. Based on the above data, less invasive alternative therapeutic interventions to avoid short- and long-term adverse events of surgery are needed. In this context radiofrequency ablation has been reported to be effective in the treatment of these tumors in absence of major adverse events. However, the available studies on the matter are limited by small sample size and lack of standardized criteria for patient selection.

Official Title
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Safety and Efficacy of Endoscopic Ultrasound-guided RadioFrequency Ablation for the Treatment of Functional and Non-functional Pancreatic NeuroEndocrine Neoplasms: A Multicenter Prospective Study

Conditions
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Neuroendocrine Tumors, Neuroendocrine Carcinoma, Pancreas Neoplasm, Neuroendocrine Tumor Gastrointestinal, Hormone-Secreting

Intervention / Treatment
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* Device: EUS guided radiofrequency ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For all patients Age ≥18 years and <80 years Signed written informed consent Distance from the main pancreatic duct ≥2mm Able to undergo endoscopic ultrasound examination Homogeneous enhancement at contrast harmonic EUS (CH-EUS) For patients with functional pancreatic neuroendocrine neoplasms (F-PanNENs), almost all insulinomas Definitive diagnosis of a clinical syndrome related to excessive insulin secretion fasting test, insulin blood levels, C-peptide blood levels) Single lesion visualized at CT, and/or MRI, and/or EUS Size < 20mm For patients with non functional pancreatic neuroendocrine neoplasms (NF-PanNENs) EUS fine needle biopsy (FNB) proven NF-PanNENs 68Ga-DOTATATE PET/CT positive for a pancreatic lesion and negative for lymph nodes, liver, and other distant metastases Hyper- or Iso-enhancing pattern at MRI and/or CT with negative lymph nodes, liver, and other distant metastases G1 or G2 ≤ 5% on histological examination of EUS-guided biopsy samples utilizing EUS-FNB needles Diameter between 15mm and 25mm, Absence of symptoms Absence of inner calcifications Exclusion Criteria: For all patients Known bleeding disorder that cannot be sufficiently corrected with co-fact or fresh frozen plasma (FFP) Use of anticoagulants that cannot be discontinued INR >1.5 or platelet count <50.000 Previous inclusion in other studies Pregnancy Minimal distance from the main pancreatic duct <1mm Inability to sign the informed consent Heterogeneous enhancement at contrast harmonic EUS (CH-EUS) For patients with F-PanNENs (almost all insulinomas) Diagnosis work up negative excessive hormone secretion syndrome Multiple lesions visualized at CT, and/or MRI, and/or EUS Size > 20mm For patients with NF-PanNENs G2>5% or G3 on histological examination of EUS-guided biopsy samples Diameter <15 mm and >25 mm Presence of symptoms Presence of calcifications Hypo-enhancing pattern at MRI and/or CT 68Ga-DOTATATE PET/CT positive for lymph nodes, liver, and other distant metastasis Diagnosis on multiple endocrine neoplasia type 1 (MEN1) syndrome or Von Hippel Lindau syndrome Previous inclusion in other studies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EUS guided radiofrequency ablation<br>Radiofrequency ablation will be performed using a system that consists of an 19-gauge needle electrode (140-cm long), a radiofrequency generator, and an inner cooling system that circulates chilled saline solution during the RFA procedure. | Device: EUS guided radiofrequency ablation<br>* The EUS-RFA system (Taewoong, Seoul, Korea) utilized for EUS-RFA consists of an 19-gauge needle electrode (140-cm long), a radiofrequency generator, and an inner cooling system that circulates chilled saline solution during the RFA procedure. The inner metal part is insulated over its entire length, with the exception of the terminal 5 to 20mm for energy delivery. The needle electrode is attached to a radio frequency current generator (VIVA RF generator; Taewoong) and to a cooling pump. The generator, in addition to providing radio frequency current, allows the control of physical power and impedance parameters.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) after EUS-guided radiofrequency ablation (RFA) | AEs will be classified as procedural when they occur during the procedure; post-procedural when they will occur up to 14 days after the procedure; late when they will occur more than 14 days after the procedure. Minor AEs will be those that need no therapy and have no sequelae (A) or have minor therapy or consequence, including overnight admission (B). Major events include those that require major therapy or hospitalization (24- 48 hours) (C); major therapy, need unplanned increase in level of care, or hospitalization >48 hours (D); or result in permanent adverse sequelae (E) and death (F). | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of secondary surgery | Number of patients who will require secondary surgey due to adverse events occurence, no response/failed or partial/recurrence outcome to the RFA treatment | 1 year |