Endoscopic Ultrasound Radiofrequency Ablation for GISTs

Study Overview
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Brief Summary
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Nowadays, for the selection of the treatment for gastrointestinal stromal tumors (GISTs), tumor size, prognosis, resectability and stage should be considered. Due to mutations in KIT and platelet-derived growth factor alpha (PDGFRA) in 90% of patients with this mesenchymal tumor, many tyrosine kinase inhibitors are used. On the other hand, a resectable tumor is approached by surgery, endoscopic and ablation therapy. Radiofrequency ablation (RFA) approach has been studied in hepatic GISTs, and hepatic metastases, but its evaluation in esophageal, gastric, and intestinal GISTs is scarce. This study aims to determine the feasibility, safety and efficacy of endoscopic ultrasound (EUS) guided RFA using the 19 G RFA probe developed by Taewong Medical for the treatment of GISTs.

Detailed Description
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Gastrointestinal stromal tumors (GISTs) are the most common malignant mesenchymal tumors of the gastrointestinal tract. GISTs usually appear like subepithelial lesions covered by normal mucosa, arising from the second of fourth layer of the gastrointestinal tract wall. They are variable in size and mostly asymptomatic, but they can present different clinical behavior as bleeding, pain, or obstruction. The tumor size, location and mitotic rate are important prognostic factors. For resectable tumors >2 cm, surgery is the treatment of choice; the management of tumors <2 cm remains debatable because they present unclear clinical significance and low risk of malignancy. Endoscopic treatment, when complete resection it's possible, could be an option to full thickness laparoscopic resection. Moreover, around 90% of GISTs harbour driver mutation in KIT and platelet-derived growth factor alpha (PDGFRA), making the treatment with tyrosine kinase inhibitors (i.e., imatinib, sunitinib and regorafenib) a suitable option for locally advanced and metastatic disease. Nevertheless, the role of local treatment in advanced and metastatic disease is limited, with few retrospective studies suggesting tumor ablation as a therapeutic approach. According to literature, thermal ablation has been successfully used for local treatment of hepatic metastases from GISTs (as a curative treatment). However, its feasibility and technical success as a local treatment in esophageal, gastric or intestinal GISTs has not been evaluated. The investigators aimed to determine the feasibility and efficacy of the RFA electrode developed by Taewong Medical for the treatment of resectable GISTs (esophageal, gastric and intestinal lesions) as well as its limited liver metastases in naïve patients or patients with stable disease following systemic therapy with tyrosine kinase inhibitors. The challenge is whether to introduce local ablative therapy as curative or as part of multimodal treatment in patients with GISTs to obtain a curable disease and an increase in overall survival for metastatic patients.

Official Title
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Feasibility, Safety, and Efficacy of EUS-guided Thermal Radiofrequency Ablation in the Treatment of Gastrointestinal Stromal Tumors

Conditions
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Gastrointestinal Stromal Tumor (GIST)

Intervention / Treatment
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* Procedure: Endoscopic ultrasound guided radiofrequency ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults (> 18 years of age) Confirmed resectable GISTs lesions in esophagus, stomach, and intestine (between 2<5 cm or 5-10cm and <5mitotes/HPF) Non-amenable to surgery written informed consent No evidence of metastatic disease on imaging of the chest abdomen and pelvis contrast enhanced computed tomography (CE-CT) or limited liver metastatic disease (maximum 5 lesions <= 3 cm) Adequate renal, hepatic, and hematological function Exclusion Criteria: Pregnancy Rectal GISTs Altered renal, hepatic, or hematological function Inability to provide informed consent Patients with cardiac pacemakers or other implanted electronic devices and/or electrodes Patients that have right-to-left shunts, severe pulmonary hypertension (pulmonary artery pressure >90 mmHg), uncontrolled systemic hypertension, and in patients with adult respiratory distress syndrome or any condition that contraindicates the procedure Inability to tolerate general anesthesia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 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
Interventional Model Description: A non-blinded, single center, non-randomized prospective feasibility trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EUS guided RFA<br>This group is comprised by patients with diagnosis of resectable GISTs with/without liver metastasis. The patients included are naïve (without previous treatment) or patients with stable/progressive disease following systemic therapy with tyrosine kinase inhibitors. | Procedure: Endoscopic ultrasound guided radiofrequency ablation<br>* Patients will be first assessed by DFI-EUS and CE-EUS. Then. EUS guided RFA will be performed using the 19G electrode ablation needle connected to the Starmed radiofrequency generator (Taewong Medical, Seoul, South Korea). After EUS identification of the GIST, a place without interposing vessels will be found by the endosonographer. Puncture of the tumor will be performed directly with the ablation probe inserted through the working channel of the echoendoscope. Time - seconds will depend by the tumor dimension, localization, distance from vital structures (e.g., aorta) and EUS appearance (e.g., hyperechoic). Power will be set at no more than 30W. If the tumor is in contact with vital structures a 10mm safe margin will be kept from these to avoid thermal injury. Multiple applications can be performed in the same or separate session depending on the residual tumor tissue evaluated with DFI-EUSor CE-EUS immediately after procedure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | Incidence of adverse events of EUS guided RFA for GISTs' lesions and metastasis. Data will be summarized as frequencies and relative frequencies. | up to 6 months | 
| Technical success of RFA of GISTs lesions and metastasis | The technical success will be assessed by completion of ablation on EUS by the time of the procedure, indicated by replacement of the lesion by structural/appearance changes on DFI and CE-EUS Data will be summarized as frequencies. | up to 2 hours | 
| Disease-free survival | Will be assessed by measuring the proportion of patients demonstrating absence of residual tumor on follow-up. CT- scan and DFI at one, three and six months will be performed to evaluate tumor response to the treatment. Will be estimated with a Kaplan-Meier estimator and curve. Estimates will be given for specific time points along with 95% confidence intervals. | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Re-treatment rate | Proportion of patients needing re-treatment for residual tumor in a one-month period after the intervention. | 1-month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastrointestinal stromal tumor, Radiofrequency, Endosonography