The Use of Biomarkers to Guide Management of Patients Treated With Radiofrequency Ablation for Early Oesophageal Neoplasia
- Conditions
- Barrett's Oesophagus
- Interventions
- Diagnostic Test: Cytosponge testDiagnostic Test: Oesophagogastroduodenoscopy
- Registration Number
- NCT04155242
- Lead Sponsor
- University of Cambridge
- Brief Summary
This prospective cohort study aims to assess the utility of a panel of molecular biomarkers for predicting the risk of relapse of Barrett's Oesophagus after endoscopic treatment of early oesophageal neoplasia with RadioFrequency Ablation (RFA). Patients who received endoscopic treatment of early oesophageal neoplasia with RFA and achieved endoscopic remission will be recruited. During the surveillance visits patients will receive a Cytosponge test followed by an endoscopy with Narrow Band Imaging (NBI) magnification and biopsies. Patients will receive an endoscopy every 6 months and Cytosponge every 12 months for at least 2 years. Molecular biomarkers including a methylation panel on DNA and immunohistochemical markers on formalin fixed paraffin embedded samples. After 2 years of intensive endoscopic follow up, patients will be prospectively tracked for up to 3 years.
The investigators will also evaluate:
* The risk of progression to dysplasia or oesophageal intestinal metaplasia (IM) in patients with IM at the GOJ post RFA in the absence of retreatment
* the diagnostic accuracy of NBI for IM/dysplasia at the GOJ .
- Detailed Description
The panel of predetermined molecular biomarkers includes:
1. IM-SCORE - a score quantifying the extent of intestinal metaplasia at GOJ, which uses a 4-tier system based on the number of glands and the number of biopsies with features of IM. The score has been developed in a pilot study (manuscript under submission) and will be validated in this study
2. Methylation markers- assessed by a PCR-based method (Methylight) on Cytosponge samples.
3. P53 status.
4. TFF3 protein expression.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 147
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Study group Cytosponge test As part of the post RFA treatment follow up patients will receive a Cytosponge test followed by an endoscopy with NBI magnification and biopsies. Four endoscopies will be performed during 2 years of active follow up together with up to 2 Cytosponge procedures. Molecular biomarkers including a methylation panel on DNA and immunohistochemical markers on formalin fixed paraffin embedded samples obtained during the examinations will be assessed. Patients will be then followed up for up to 3 years with standard endoscopy to assess for relapse of Barrett's oesophagus/IM/dysplasia. Study group Oesophagogastroduodenoscopy As part of the post RFA treatment follow up patients will receive a Cytosponge test followed by an endoscopy with NBI magnification and biopsies. Four endoscopies will be performed during 2 years of active follow up together with up to 2 Cytosponge procedures. Molecular biomarkers including a methylation panel on DNA and immunohistochemical markers on formalin fixed paraffin embedded samples obtained during the examinations will be assessed. Patients will be then followed up for up to 3 years with standard endoscopy to assess for relapse of Barrett's oesophagus/IM/dysplasia.
- Primary Outcome Measures
Name Time Method Diagnostic accuracy of methylation panel for diffuse IM at the GOJ 5 years Diagnostic accuracy of a panel of methylation markers (ZNF345, ZNF569 and TFPI2 loci) for diffuse IM at the GOJ assessed by Methylight on DNA extracted from GOJ biopsies (separately random and targeted biopsies) and Cytosponge samples.
- Secondary Outcome Measures
Name Time Method Proportion of patients developing true BE recurrence 5 years Number of patients with GOJ IM with different IM score that will develop true BE recurrence during the observation period defined as oesophageal IM or dysplasia.
Biomarker score for BE recurrence 5 years The accuracy of a biomarker panel to predict risk of BE recurrence. The following biomarkers will be assessed:
* P53 status by immunohistochemistry
* TFF3 expression by immunohistochemistry
* IM-SCORE (defined in the Study Description section)
* methylation markers (defined in the Outcome 1 Description section).Safety of Cytosponge 5 years Number of participants with Cytosponge procedure-related serious adverse events defined as an event that:
Results in death Is life-threatening Requires hospitalisation or prolongation of existing hospitalisation Results in persistent or significant disability or incapacity Consists of a congenital anomaly or birth defect Is otherwise considered medically significant by the investigator (eg. a further procedure is required for the patient).Accuracy of Light Blue Crest sign 5 years Diagnostic accuracy of a Light Blue Crest (LBC) sign in NBI for the diagnosis of GOJ IM. During each performed endoscopy, NBI magnification will be used to assess systematically the mucosal pit pattern at the GOJ and to look for the LBC sign. In order to assess the accuracy of LBC, targeted biopsies will be taken from all the areas with LBC.
Trial Locations
- Locations (1)
MRC Cancer Unit
🇬🇧Cambridge, United Kingdom