RFA to Prevent Metachronous Squamous Neoplasia Recurrence After Complete Endoscopic Submucosal Dissection

Study Overview
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Brief Summary
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Esophageal cancer is a highly lethal disease, and its incidence is still increasing in the world. Recent advances in image-enhanced techniques such as Lugol chromoendoscopy and narrow band imaging, the number of patients with early esophageal squamous cell neoplasias (ESCNs) detected has markedly increased. Endoscopic submucosal dissection (ESD) enables en bloc resection of the neoplasia, and the resected specimen allows for a pathological assessment to evaluate the curability. However, the patients who received complete ESD for early ESCNs frequently developed metachronous recurrence. The cumulative metachronous recurrence rate at 5 years was 50%, and the mean annual incidence of newly diagnosed metachronous tumors was 10%. Among them, those with speckled lugol staining pattern over the esophageal background mucosa have the highest risk and should be seen as a precancerous lesion of ESCCs. This issue is gaining attention in the era of endoscopic treatment, but currently there was no appropriate strategy to prevent the tumor recurrence in these high-risk subjects. Endoscopic radiofrequency ablation (RFA) is a rapidly evolving therapeutic modality, and recent studies have shown its efficacy and safety for eradicating for flat type early ESCNs. To search a best strategy for the prevention of ESCNs, the investigators thus propose a hypothesis that the preemptive RFA for esophageal speckled lugol background mucosa may prevent the metachronous neoplastic recurrence after complete endoscopic resection.

Official Title
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Preemptive Radiofrequency Ablation for Esophageal Speckled Lugol Background Mucosa to Prevent Metachronous Neoplastic Recurrence After Complete Endoscopic Submucosal Dissection  A Randomized Controlled Study

Conditions
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Esophageal Squamous Cell Neoplasm

Intervention / Treatment
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* Procedure: Radiofrequency ablation
* Device: Endoscopy
* Drug: Lugol's Solution (1.5%)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults with early stage ESCNs (squamous high grade dysplasia, carcinoma in situ, or T1N0M0 SCC) who were treated by endoscopic submucosal dissection. Lugol staining showed speckled (>10 small lugol-unstained lesions) pattern of background mucosa. Exclusion Criteria: Having a history of incomplete endoscopic treatment, or complications during/after treatment (perforation, stricture). Having history of systemic chemotherapy or radiation therapy for esophagus or post esophagectomy. Life expectancy <2 yr. Decompensated cirrhosis (Child score B, C). Having large esophageal varices. Poor performance status (ECOG>2).

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 90 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RFA group<br>Balloon type RFA (12J/cm2, 1 application) will be applied for the entire speckled esophageal mucosa at the 3 months after complete ESD. Oral prednisolone 30mg/day will be prescribed at day 3 after RFA procedure and continue for 28 days to prevent the post-RFA stenosis. | Procedure: Radiofrequency ablation<br>* HALO360 System (Covidien GI Solutions, Sunnyvale, California, USA), which has been approved by the US Food and Drug Administration (FDA) and is approved for use in Europe (CE mark) and Taiwan (Ministry of Health and Welfare). Because the HALO 360 balloon catheter has been phased out since 2019, a new Barrx™ 360 Express catheter was used thereafter.<br>Device: Endoscopy<br>* The participants will receive meticulous endoscopic examination with Lugol chromoendoscopy and Narrow-band imaging<br>Drug: Lugol's Solution (1.5%)<br>* Before the RFA intervention, the participants will received Lugol staining over the esophagus<br>|
| No Intervention: Control group<br>No intervention; surveillance endoscopy alone | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor recurrence | Metachronous tumor recurrence is defined as a tumor (high-grade dysplasia or squamous cell carcinoma) recurring at a new site after more than 6 months of complete remission status. | From date of randomization until the date of first documented tumor recurrence, assessed up to 100 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse events | including perforation, dysphagia, stenosis, defined as the failure of a standard endoscope (9.8 mm in diameter) to pass through the stenosis, or others resulting in the patients intolerable and discontinued intervention. | From date of intervention until the date of first documented adverse events, assessed up to 12months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Early esophageal squamous cell neoplasm, Radiofrequency ablation, Endoscopic submucosal dissection, Esophageal cancer, Recurrence, Field cancerization